EP0091277B1 - Dimethylacetamide solvate of syn-(2-amino thiazol-4-yl)(methoxyimino)acetic acid - Google Patents
Dimethylacetamide solvate of syn-(2-amino thiazol-4-yl)(methoxyimino)acetic acid Download PDFInfo
- Publication number
- EP0091277B1 EP0091277B1 EP83301807A EP83301807A EP0091277B1 EP 0091277 B1 EP0091277 B1 EP 0091277B1 EP 83301807 A EP83301807 A EP 83301807A EP 83301807 A EP83301807 A EP 83301807A EP 0091277 B1 EP0091277 B1 EP 0091277B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- solvate
- acetic acid
- syn
- dimethylacetamide
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 title claims description 50
- 239000012453 solvate Substances 0.000 title claims description 33
- MIHIJWOEDDPOLG-RQOWECAXSA-N (2z)-2-methoxyiminoacetic acid Chemical compound CO\N=C/C(O)=O MIHIJWOEDDPOLG-RQOWECAXSA-N 0.000 title claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 23
- -1 methoximino Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000012535 impurity Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000003109 Karl Fischer titration Methods 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229950003476 aminothiazole Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 150000004816 dichlorobenzenes Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- 229940115425 methylbenzyl acetate Drugs 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/587—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with aliphatic hydrocarbon radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms, said aliphatic radicals being substituted in the alpha-position to the ring by a hetero atom, e.g. with m >= 0, Z being a singly or a doubly bound hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
Definitions
- This invention concerns synthetic pharmaceutical chemistry. It provides a new solvate and makes available a new process for purifying syn-(2-aminothiazol-4-yl)(methoxyimino)acetic acid using the solvate.
- Syn-(2-aminothiazol-4-yl)(methoxyimino)acetic acid is a known compound. It is used as an intermediate in preparing cephalosporin pharmaceuticals of the type having an acyl side chain formed from the thiazolyl acetic acid. Numerous patents and publications disclosing this use have appeared. For example, U.S. Patent 4,152,433 of Fujisawa Co. and U.S. Patent 4,098,888 of Takeda Chemical Industries show the synthesis of various cephalosporin compounds making use of the thiazolylacetic acid as an intermediate. Often the amino group of the substituted acetic acid is blocked by a group such as trityl or the like, and the acid is usually converted into an active form such as the acid chloride or the like for use as an acylating agent.
- solvates are known to be a highly individualistic effect. The ability of a given compound to form a solvate is not predictable, so far as applicant knows, and to his knowledge and belief nothing in the literature indicates that syn-(2-aminothiazol-4-yl)(methoxyimino)acetic acid can form a solvate with dimethylacetamide, or with any solvent.
- this invention provides a dimethylacetamide solvate of syn-(2-aminothiazol-4-yl)-(methoxyimino)acetic acid containing 2 moles of dimethylacetamide per mole of the acid.
- the thiazolyl acetic acid whose solvate is provided by this invention is of the formula It is important that the methoxyimino group be in the configuration shown, known as the syn configuration, because it is now well known that the cephalosporins formed from the acid are much more biologically active when the imino group is in the syn configuration.
- the dimethylacetamide (DMAC) disolvate of the acid is readily formed by merely dissolving the impure solid acid in DMAC, and crystallizing the solvate from the solution.
- the crystallization may be done by the usual methods, such as cooling or chilling a solution made at an elevated temperature, or evaporating part of the DMAC from the solution.
- the formation of the DMAC disolvate is a simple crystallization from DMAC.
- the formation and precipitation of the disolvate are analogous to other crystallization procedures.
- the yield of disolvate is increased by higher concentration of the acid and by lower crystallization temperature, and decreased by lower concentration and higher crystallization temperature.
- the composition and purity of the precipitated disolvate are not affected by the conditions, however. Accordingly, the chemist can vary the amount of DMAC and the temperatures freely. For example, concentrations of the acid in the range of from about 5% to about 50% by weight may be used as may be desired in a given case.
- the DMAC solution of the acid may be heated, to obtain dissolution, to temperatures in the range of from about the ambient temperature to about 100°C, or even higher, using elevated pressures as necessary to suppress boiling.
- the solution may be cooled, to obtain crystallization, to any temperature short of that which completely solidifies the solution, such as from about -50°C to about the ambient temperature.
- a process for preparing a dimethylacetamide solvate of syn-(2-aminothiazol-4-yl)(methoxyimino)acetic acid the solvate containing 2 moles of dimethylacetamide per mole of acid, which comprises dissolving impure syn-(2-aminothiazol-4-yl)-(methoxyimino)acetic acid in dimethylacetamide and crystallizing the solvate.
- the precipitated disolvate is easily removed from the liquid phase by filtration or centrifugation, and can be washed on the filter with DMAC or other solvents to remove liquid phase containing the impurities which have been removed from the acid.
- the solvate of this invention is a true solvate having a fixed composition, but it is not tightly bound.
- the DMAC is easily removed from the solvate with heat and vacuum, if the dry pure acid is needed for use as an intermediate.
- the solvent for the next synthetic step is DMAC, or if a small amount of DMAC is acceptable in the reaction mixture, the solvate may be used as the intermediate without further treatment.
- the DMAC is readily removed from the solvate of this invention by simple contact with water, or with virtually any convenient organic solvent. It is unnecessary to dissolve the solvate to remove the DMAC. As the examples below illustrate, mere slurrying of the solvate in an organic solvent or water will remove the DMAC into the solvent phase, so that the acid may be obtained in pure form by filtering.
- ethers such as diethyl ether, tetrahydrofuran and diisopropyl ether, alcohols such as methanol, ethanol and butanol, alkanes such as hexane, octane and the like, haloalkanes such as dichloromethane, 1,2-dichloroethane and trichloroethane, aromatics and halo-aromatics such as benzene, toluene, xylene, chlorobenzene, bromobenzene and the dichlorobenzenes, amides such as dimethylformamide, and ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone may be used.
- a process for purifying syn-(2-aminothiazol-4-yl)(methoxyimino)acetic acid comprising dissolving impure syn-(2-aminothiazol-4-yl)-(methoximino)acetic acid in dimethylacetamide, crystallizing the dimethylacetamide solvate, removing the solvate from the solution, and removing the dimethylacetamide from the solvate.
- the method of purification is especially useful for purifying water-wet acid. It is found that water is particularly difficult to remove from the acid, and normal drying techniques are inadequate.
- the purification method of this invention precipitates the disolvate quite free of water, even when the impure acid contains several percent of water, and accordingly produces the acid in a form which is much more appropriate for further processing.
- the present method also is particularly efficient in purifying the acid from the dark, tarry contaminants which usually are formed in its synthesis.
- the solvate precipitates as cubic white crystals, leaving the dark matter in the DMAC phase. It will be understood that dark-colored impurities are very undesirable in intermediates to be used for synthesis, especially in pharmaceutical intermediates.
- the solvate may be used as an intermediate, just as it is precipitated, if a small amount of DMAC is . acceptable in the reaction mixture in which it is to serve as an intermediate. If DMAC is not acceptable, the DMAC can be removed by drying, or displaced with water, if the next reaction mixture is aqueous, or with any convenient organic solvent, if water is not acceptable in that next reaction mixture.
- the disolvate was suspended in 400 ml of ethyl acetate and stirred for 2 hours at 45°C under nitrogen. The suspension was then cooled to 10°C and filtered, and the solids were washed with 800 ml of additional ethyl acetate. The washed solids were dried for two and a half hours in air at 50°C, and 44.4 g of dried product was obtained, which was identified as 97.26% pure syn-(2-aminothiazol-4-yl)(methoximino)acetic acid containing 1.35% of DMAC and 1.37% of ethyl acetate. The water content of the product was 0.36% by Karl Fischer analysis. M.P. 130-131 0 C.
- the solid disolvate was washed with 200 ml of 1:4 DMAC:ethyl acetate, 200 ml of 1:19 DMAC:ethyl acetate and finally with 400 ml of ethyl acetate.
- the solid disolvate was perfectly white and the cake was crystalline and easily handled. M.P. 60-66°C.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/364,356 US4426528A (en) | 1982-04-01 | 1982-04-01 | Purification of syn-(2-aminothiazol-4-yl)methoxyimino)acetic acid |
| US364356 | 1982-04-01 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0091277A2 EP0091277A2 (en) | 1983-10-12 |
| EP0091277A3 EP0091277A3 (en) | 1984-12-27 |
| EP0091277B1 true EP0091277B1 (en) | 1987-06-16 |
Family
ID=23434150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP83301807A Expired EP0091277B1 (en) | 1982-04-01 | 1983-03-30 | Dimethylacetamide solvate of syn-(2-amino thiazol-4-yl)(methoxyimino)acetic acid |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4426528A (OSRAM) |
| EP (1) | EP0091277B1 (OSRAM) |
| JP (1) | JPS58183678A (OSRAM) |
| KR (1) | KR840004090A (OSRAM) |
| CA (1) | CA1194487A (OSRAM) |
| DE (1) | DE3372096D1 (OSRAM) |
| DK (1) | DK91383A (OSRAM) |
| GB (1) | GB2119370B (OSRAM) |
| GR (1) | GR79243B (OSRAM) |
| HU (1) | HU186271B (OSRAM) |
| IL (1) | IL68251A (OSRAM) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6124580A (ja) * | 1984-07-12 | 1986-02-03 | Shionogi & Co Ltd | アミノチアゾリルグルタル酸誘導体の製造方法 |
| AU2002222553A1 (en) * | 2000-12-04 | 2002-06-18 | Fujisawa Pharmaceutical Co. Ltd. | Process for producing anhydride of aminothiazole derivative |
| CN111548323B (zh) * | 2020-05-29 | 2022-06-10 | 山东金城医药化工有限公司 | 氨噻肟酸的回收方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3925372A (en) | 1973-02-23 | 1975-12-09 | Lilly Co Eli | Alpha-aminoacyl-3-halo cephalosporins |
| DK154939C (da) | 1974-12-19 | 1989-06-12 | Takeda Chemical Industries Ltd | Analogifremgangsmaade til fremstilling af thiazolylacetamido-cephemforbindelser eller farmaceutisk acceptable salte eller estere deraf |
| DE2760123C2 (de) | 1976-01-23 | 1986-04-30 | Roussel-Uclaf, Paris | 7-Aminothiazolyl-syn-oxyiminoacetamidocephalosporansäuren, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen |
| US4152433A (en) | 1976-03-12 | 1979-05-01 | Fujisawa Pharmaceutical Co., Ltd. | 2-Lower alkyl-7-substituted-2 or 3-cephem-4-carboxylic acid compounds and pharmaceutical compositions |
| DK162391C (da) * | 1976-04-12 | 1992-03-09 | Fujisawa Pharmaceutical Co | Analogifremgangsmaade til fremstilling af syn-isomerer af 3,7-disubstituerede 3-cephem-4-carboxylsyreforbindelser |
| US4252951A (en) | 1979-10-09 | 1981-02-24 | Eli Lilly And Company | Isolation of syn-7-(2-amino-4-thiazolyl)-(methoxyimino)acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid |
| JPS58135872A (ja) * | 1981-11-13 | 1983-08-12 | グラクソ・グル−プ・リミテツド | 新規な化合物およびその製法 |
-
1982
- 1982-04-01 US US06/364,356 patent/US4426528A/en not_active Expired - Fee Related
-
1983
- 1983-02-25 DK DK91383A patent/DK91383A/da not_active Application Discontinuation
- 1983-03-28 IL IL68251A patent/IL68251A/xx unknown
- 1983-03-28 CA CA000424616A patent/CA1194487A/en not_active Expired
- 1983-03-29 GR GR70925A patent/GR79243B/el unknown
- 1983-03-30 KR KR1019830001295A patent/KR840004090A/ko not_active Withdrawn
- 1983-03-30 EP EP83301807A patent/EP0091277B1/en not_active Expired
- 1983-03-30 JP JP58056821A patent/JPS58183678A/ja active Pending
- 1983-03-30 DE DE8383301807T patent/DE3372096D1/de not_active Expired
- 1983-03-30 GB GB08308858A patent/GB2119370B/en not_active Expired
- 1983-03-31 HU HU831119A patent/HU186271B/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB2119370B (en) | 1985-06-05 |
| GB2119370A (en) | 1983-11-16 |
| JPS58183678A (ja) | 1983-10-26 |
| GR79243B (OSRAM) | 1984-10-22 |
| DE3372096D1 (en) | 1987-07-23 |
| IL68251A (en) | 1986-03-31 |
| DK91383A (da) | 1983-10-02 |
| HU186271B (en) | 1985-07-29 |
| US4426528A (en) | 1984-01-17 |
| EP0091277A2 (en) | 1983-10-12 |
| DK91383D0 (da) | 1983-02-25 |
| KR840004090A (ko) | 1984-10-06 |
| CA1194487A (en) | 1985-10-01 |
| EP0091277A3 (en) | 1984-12-27 |
| IL68251A0 (en) | 1983-06-15 |
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